Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction

Abstract

In this study, we report a convenient and high yielding formal semisynthesis of demethylgorgosterol, a marine steroid with an intriguing sidechain containing a cyclopropane unit. This was achieved through the synthesis of an advanced ketone intermediate. The synthetic route features a total of ten steps, starting from commercially available stigmasterol, with an overall yield of 27 %. The key step was a stereoselective intermolecular cyclopropanation reaction. This reaction proceeded in 82 % yield, the resulting cyclopropane carboxylic ester shows a trans/cis ratio of 89 : 11, with a diastereomeric ratio for the trans-diastereomers of >99 : 1. A reduction/oxidation sequence afforded the corresponding aldehyde, which was used in a Grignard reaction. A final oxidation step then yielded the desired ketone. This novel route presents a platform to further investigate the medicinal applications of gorgosterol-type steroids and to fully understand their role in coral symbiosis.